Genetic screening could soon offer hope for families affected by an inherited form of stomach cancer, following research published this week by Cancer Research UK scientists1.
Researchers have found that a rare form of stomach cancer – affecting 200 people in the UK each year – is often caused by the inheritance of a faulty gene. They were able to detect the damaged gene in a third of families with a history of the disease.
Screening in this way could save lives, by giving affected people the chance of life-saving pre-emptive surgery. And understanding how the damaged gene causes stomach cancer will give scientists vital information about more common, non-inherited forms of the disease.
Of the 10,500 cases of stomach cancer in the UK each year, about 10 per cent run in families. The disease normally affects the over sixties, but inherited forms strike much earlier, usually before the age of 40. Since survival is very poor, it’s vital that scientists identify those at highest risk and try to prevent the disease.
Dr Carlos Caldas and his team at the Cancer Research UK Department of Oncology, Cambridge University, studied a form of the disease called hereditary diffuse gastric cancer (HDGC). Researchers looked at 39 families with a history of stomach cancer from nine different countries, including the UK. Eleven of the families were affected by HDGC while the rest had various other inherited types.
Scientists took blood samples from several cancer patients in each family and used them to analyse the E-cadherin gene, which is involved in helping cells bind together in tissues. When it goes wrong, cancers like HDGC, in which tumour cells spread rapidly outwards, can develop.
In four of the 11 HDGC families, the patients had faulty versions of the E-cadherin gene. But none of the patients with other forms of stomach cancer had the fault, suggesting that it is exclusive to this particular type.
Dr Caldas says: “People with a faulty E-cadherin gene have a 60-80 per cent chance of developing stomach cancer at some stage of their life, with many getting it very young. It’s not an easily treated disease and survival is very poor.”
“But if we can screen for the damaged gene, those affected could have surgery to prevent the disease. This may be a difficult option to take, but it’s preferable to having a very high chance of dying young from cancer.”
Researchers estimate that about 200 people develop HDGC in the UK each year. The majority of these will have the disease in their family, which means that they could easily be identified as being eligible for screening.
Dr Caldas says: “We know that the gene is damaged in about a third of HDGC families, but apparently in none with other forms of inherited stomach cancer. That makes it simpler to screen because you’ve got a self-selecting target group and a high chance of a positive test.”
Dr Caldas now intends to extend his research to look at other genes that may increase the risk of stomach cancer. He hopes that the success of his current work will encourage people with a family history of the disease to volunteer themselves for large scale clinical studies.
Many of the same genes responsible for inherited cancers also go wrong within tumours in non-hereditary forms of the disease, which means that the new results could have wide-ranging implications.
Sir Paul Nurse, Interim Chief Executive of Cancer Research UK, says: “Often genes which go wrong in hereditary cancers can play an important role in other forms of the disease as well. Learning more about the way these genes work is therefore vital for the better understanding of cancer.”
He adds: “This work is extremely important, because it offers a way of testing for those at very high risk of stomach cancer. It’s a very difficult disease to cure so prevention is a much more attractive option.”
- Human Mutation19 (5) pp. 510-517